A Comparison Between the Effect of Cuminum Cyminum and Vitamin E on the Level of Leptin, Paraoxonase 1, HbA1c and Oxidized LDL in Diabetic Patients.

Diabetes is one of the most common metabolic diseases in the world. Vitamin E reduces protein glycation and improves insulin sensitivity, while cumin is effective in remission of diabetes. Therefore this study was designed to evaluate the effects of vitamin E and cumin essential oil, on the blood level of leptin,glycosylated hemoglobin (HbA1C) and also on lipid profile in diabetic patients.In this double blind clinical trial, 95 diabetic patients were selected and randomly dividedinto three groups.The first group received cumin essential oil in capsule form. The second group received Vitamin E, and the third group was used ascontrol receiving oral gelatin capsules as placebo for three months period.Blood glucose, lipid profile, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), leptin, HbA1c, oxidized LDL (oxLDL), and paraoxonase1 activity were measured. The results showed reduction in oxLDL and significant increase in paraoxonase 1 in Vitamin E group by the end of the third month period (P<0.05). Cumin group showed decrease in blood glucose, HbA1C, triglyceride, leptin and ox-LDL. ApoA1 and paraoxonase1 were also increased by cumin treatment (P<0.05).Diabetic complications may have been reduced by intake of Vitamin E and cumin essential oil. Cumin in comparison with vitamin E has broader impact and it is more beneficial in terms of ability to reduce the diabetic index.

corresponding receptor (4). Vitamin E reduces the oxidation of lipoproteins, oxidative damage of the endothelium, proteins glycation, and consequently improves insulin sensitivity (5). Some studies have shown that low levels of vitamin E are directly associated with diabetes, causing diabetes complications (6). There are contradictory data on the effect of vitamin E on insulin and blood sugar (7).
Cumin is an herbaceous aromatic plant, yearlong; in the Apiaceae family with the scientific name of "cuminum cyminum". Cumin is harvested in Iran and it is used in traditional medicine, drinks flavor and desserts, and also as a fragrant component in creams, lotions and perfumes.Cumin is used in the treatment of various diseases and is effective in remission of diabetes. The fruit of cumin contains 2-5% essential oil which is mainly made of paracetamol, alpha and beta pinene, propanal, cumin alcohol, cuminaldehyde, alpha terpineol and myrcene (8).
In a study comparing the anti-diabetic efficacy of cumin and glibenclamide, cumin effects in preventing the free radical formation, decreasing glucose and protein glycation end products was very much improved in comparison with glibenclamide (9). In another study, the impact of cumin on blood glucose and oxidized LDL (oxLDL) decrease, and increase in arylesterase activity of paraoxonase 1 was reported (10).
Increased activity of paraoxonase 1 induces an increase in the concentration of HDL in serum, confirming that increased paraoxonase 1 activity leads to less cardiovascular disease in humans (11).
The present study was designed to evaluate the effect of vitamin E and cumin essential oil, on blood leptin, HbA1c and lipid profile of diabetic patients.

Patient selection and sampling
This study was approved by the Medical Research supplements and drug users, were excluded from the study. Ten patients including 6 and 3 subjects from cumin and vitamin E groups respectively, and also one subject from control group, withdrew during the study.The laboratory data as well as questionnaires data were collected for analysis.

Study design
The patients were randomly assigned into 3 groups. The first group received cumin essential oil(in capsules resembling placebo and vitamin E capsules), the second group received vitamin E and the third group served as control and received oral gelatin capsules as placebo for a period of 3 months. Dosage of vitamin E was based on a similar study (12) and after approval by the physician, 800 IU (150 mg) was selected. Cumin dosage was determined as 25 mg/day according to the manufacturer's instructions. At the beginning of the study and after 90 days of intake of supplements in each group, 10 ml venous blood in fasting state was collected from all participants. Blood serum were stored at -20°C before measuring leptin, lipid profile,paraoxonase1,levels. Whole blood containing EDTA was used HbA1c level measurement.

Biochemical analyzes
Blood glucose and lipid profile were measured using the autoanalyzer (BT-3000-Italy) and appropriate commercial kits from Pars Azmoon, Iran. Apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) were measured by immunoturbidimetry.Serum levels of leptin and oxLDL were detected by ELISA kit (Mercodia, Sweden).
HbA1c was measured using column chromatography with Nycocard Reader II.
Arylesterase activity of paraoxonase 1 was measured using phenylacetate as the substrate, by spectrophotometric method (11).

Statistical analyzes
The statistical analysis were conducted by SPSS software (version 18) using repeated measures ANOVA and independent t-test. P value <0.05 was considered as statistically significant.

Results
The demographic characteristics and age distribution of the study population are shown in table 1. There was no significant difference between the 3 groups in body mass index, sex, age and blood pressure.
Biochemical data are summarized in table 2.
As shown in this table, the results indicate adecrease in oxLDL and a significant increase in paraoxonase 1 in Vitamin E group by the end of the third month (P<0.05). Results in cumin group showed a decrease in blood glucose, HbA1C, triglyceride, leptin and ox-LDL. Apo A1 and paraoxonase1 were increased after three months cumin intake (P<0.05).

Discussion
In this study, some biochemical parameters were measured after three months of vitamin E and cumin essential oil intake by diabetic patients. The data before and after intake were compared.
Reduced level of oxLDL after vitamin E intake, is probably due to the antioxidant features of vitamin E and protective role of this vitamin in lipid oxidation,such that by reducing the quantity of oxidants, oxLDL is also reduced.
Following vitamin E intake, paraoxonase 1 enzyme activity has been increased in blood, showing that decrease in oxidative stress and oxidized lipids leads to higher enzyme activity. Our data suggest a specific relation between the increased enzyme activity and a decrease in lipid oxidation.   (20).
In the present study, the level of HDL and cholesterol showed no changes but triglycerides level was slightly reduced. It is possible that more noticeable changes would be anticipated by extended use or an increase in vitamin E dosage.
Because the intake of vitamin E has no effect on the sugar, no significant changes in HbA1c has been expected. We speculate that vitamin E has no effect in the control of dyslipidemia as no Similarly, in the present study Vitamin E did not have any effect on leptin. We speculate that genetic factors or different intake dosage of vitamin E can be the determining factors in such difference.
The present study showed that cumin essential oil intake for a period of three months caused a significant decrease in blood glucose, HbA1c, triglycerides, leptin, ox-LDL and a significant increase in paraoxonase 1 and ApoA1 concentration.
Reduction of ox-LDL can be caused by antioxidant properties of cuminum cyminum (24) and the presence of flavonoids in its composition (25). Therefore, we anticipate that increasing the amount of paraoxonase 1 as an effective antioxidant enzyme may lead to the lipid oxidation reduction.
Iron, zinc and manganese are among the components of the cuminum cyminum (26).
So it is possible that the presence of manganese in the structure of cumin helps the antioxidant enzymes such as manganese containing superoxide dismutase, to reduce the ox-LDL level.
In addition to the anti-oxidant property, cumin may have a specific effect in increasing HDL and lowering blood cholesterol, by increasing Apo A1.
Although the increase in ApoA1 has not been observed in some studies (10), but increased level of paraoxonase1 and decreased level of ox-LDL are consistent with the findings of the present study.
Some studies have reported a decrease in blood sugar, triglycerides, cholesterol and increase of HDL following cumin intake (27,28), although another research suggested that cumin has no effect on lowering the cholesterol level (29). We observed no changes in cholesterol levels, but confirmed a decrease in blood sugar and triglycerides levels.